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In a previous study of the effect of an oral contraceptive (Brown, Wells & Cunningham, 1964), urinary gonadotrophin was measured by its ability to induce ovulation in mice (Cunningham, 1962; Wells, Khosla & Brown, 1964). This method of assay, though not specific for luteinizing hormone, was considered appropriate for investigating the action of drugs which prevent ovulation. The study of two women, one through two complete menstrual cycles and the other through three, showed that treatment with a combination of norethynodrel and mestranol abolished the mid-cycle peak of gonadotrophin excretion. Before further study of the mode of action of oral contraceptives, more experience was gained with the pattern of excretion of gonadotrophin during the normal menstrual cycle measured with this assay

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J. L. Brown, D. E. Wildt, N. Wielebnowski, K. L. Goodrowe, L. H. Graham, S. Wells, and J. G. Howard

Faecal oestradiol and progestogen metabolite excretion was monitored in adult, female cheetahs (Acinonyx jubatus) (n = 26) for 1–24 months. Increased faecal oestradiol excretion was associated with mating or equine chorionic gonadotrophin (eCG) administration for artificial insemination, whereas increased progestogen metabolites were observed during natural and human chorionic gonadotrophin (hCG)-induced pregnant and nonpregnant luteal phases. On the basis of oestradiol excretory patterns, duration of the oestrous cycle (mean ± sem) was 13.6 ± 1.2 days with high oestradiol concentrations lasting for 4.1 ± 0.8 days. In non-gonadotrophin-treated cheetahs, 75% showed evidence of oestrous cyclicity; however, none evaluated for 1 year or longer were continuously cyclic. Rather, cyclicity was interrupted by periods of anoestrus, often exceeding several months in duration. These inactive ovarian periods were unrelated to season and were not synchronous among females. Mean duration of gestation (breeding to parturition) was 94.2 ± 0.5 days, whereas duration of faecal progestogen metabolite excretion during the nonpregnant luteal phase was 51.2 ± 3.5 days. On the basis of progestogen metabolite evaluations, spontaneous ovulation (non-mating induced) occurred only once in two females (2 of 184 oestrous cycles; 1.1%). Peak eCG-stimulated, preovulatory oestradiol concentrations were similar to those associated with natural oestrus, whereas progestogen metabolite profiles after hCG resembled those during pregnant and nonpregnant luteal phases after natural mating. In summary, results confirm that the cheetah is polyoestrus and ovulation is almost always induced. However, new evidence suggests that many females inexplicably experience periods of anoestrus unrelated to season, while 25% of the cheetahs examined expressed no ovarian activity during the study period.

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B A Refaat, A O Bahathiq, S Sockanathan, R L Stewart, M Wells, and W L Ledger

Fallopian tubes from ten premenopausal women were collected and examined for the presence of inhibin, activin and its type IIA and IIB receptors (ActRIIA and ActRIIB) in the endosalpinx. Immunocytochemistry demonstrated clear staining for the βA, βB subunits and ActRIIA and ActRIIB that increased in intensity from the isthmus to the ampulla. No staining for the α subunit was observed. Whilst the staining of the βA subunit and ActRIIA was seen in almost every epithelial cell, staining for the βB subunit and ActRIIB was more variable. In situ hybridization and RT-PCR confirmed the presence of mRNA for the βA, βB subunits and ActRIIA and ActRIIB. These results indicated that the epithelium of the uterine tube is able to synthesize activin but not inhibin and has receptors for activin. Activins may thus act as paracrine regulators of tubal epithelial cell function, and embryonic activity may also bind to epithelial receptor and initiate intracellular processes that alter epithelial cell secretions.

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Rodney D Geisert, Ashley E Meyer, Caroline A Pfeiffer, Destiny N Johns, Kiho Lee, Kevin D Wells, Thomas E Spencer, and Randall S Prather

Development of viviparity in mammals requires that the placenta evolves as an intermediate interface between the fetus and maternal uterus. In addition to the retention of the fetus and secretion of nutrients to support growth and development to term, it is essential that viviparous species modify or inhibit the maternal immune system from recognizing the semi-allogeneic fetus. Following blastocyst hatching from its zona pellucida, trophoblast differentiation provides the initial communication to the maternal endometrium to regulate maintenance of progesterone production from the corpus luteum and biological pathways in uterine and conceptus development necessary in the establishment and maintenance of pregnancy. Many conceptus factors have been proposed to serve in the establishment and maintenance of pregnancy. CRISPR-Cas9 gene-editing technology provides a specific and efficient method to generate animal models to perform loss-of-function studies to investigate the role of specific conceptus factors. The utilization of CRISPR-Cas9 gene editing has provided a direct approach to investigate the specific role of conceptus factors in the development and establishment of pregnancy in the pig. This technology has helped address a number of questions concerning peri-implantation development and has altered our understanding of maternal recognition and maintenance of pregnancy in the pig.